Small Intestine Hormones: Regulators of Digestion, Absorption, and Metabolism

Enteroendocrine Cells and Hormones

Specialized cells scattered in intestinal mucosa sense luminal contents and release hormones into portal/systemic circulation.

Key Hormones

Integrated Regulation

• Enterogastric reflex: CCK, secretin, GIP, GLP-1 slow gastric emptying
• Incretin effect: GIP + GLP-1 = 50–70% of postprandial insulin
• Ileal brake: Distal nutrients → PYY, GLP-1 → slow transit for absorption
• Feedback: Acid → secretin; fat/protein → CCK; carbs → GIP/GLP-1

Clinical Relevance

• GLP-1 agonists (semaglutide, tirzepatide) — diabetes, obesity
• CCK₂ agonists — pancreatitis research
• Short bowel syndrome → GLP-2 analog (teduglutide)
• Carcinoid syndrome: serotonin excess → flushing, diarrhea, valvular fibrosis

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Hormone	Cell	Location	Primary Actions
Gastrin	G	Antrum, duodenum	↑ Gastric acid (parietal), pepsin (chief); ↑ gastric motility; trophic on mucosa
CCK	I	Duodenum, jejunum	↑ Gallbladder contraction, pancreatic enzyme secretion; ↓ gastric emptying; satiety
Secretin	S	Duodenum	↑ Pancreatic/biliary bicarbonate; ↓ gastric acid; ↑ bile production
GIP	K	Duodenum, jejunum	↑ Insulin (incretin); ↑ lipid storage; weak ↓ gastric acid
GLP-1	L	Ileum, colon	↑ Insulin, ↓ glucagon, ↓ gastric emptying, ↑ satiety (incretin effect)
GLP-2	L	Ileum, colon	Intestinal growth, barrier function, nutrient absorption
PYY	L	Ileum, colon	↓ Appetite, ↓ gastric emptying, ↓ intestinal transit (ileal brake)
Motilin	M	Duodenum	Initiates MMC phase III (interdigestive housekeeping contractions)
Serotonin (5-HT)	EC	Throughout	↑ Peristalsis, secretion, visceral sensation; 95% body serotonin